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Potential role of S-adenosylmethionine in osteosarcoma development.

Shi H, Mu WD, Zhang B, Meng T, Zhang ST, Zhou DS - Onco Targets Ther (2016)

Bottom Line: The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease.In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression.At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP.

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatic Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan; Department of Bone and Joint Surgery.

ABSTRACT
The metastatic form of osteosarcoma is a life threatening one since it metastasizes to the lungs. The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease. In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression. As evidence of tumor suppression, the SAM-treated mouse tissue was analyzed histologically, which exemplifies the control that SAM has over abnormal cell proliferation, especially on primary osteosarcoma, but it lacks positive effects on metastatic osteosarcoma. At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP. The data suggest that the administration of SAM has a positive role in treating primary osteosarcoma, but it has no role in suppressing metastatic osteosarcoma. The decreased expression of Sox2 together with upregulation of TCTP following SAM administration indicates that SAM has a control over primary osteosarcoma.

No MeSH data available.


Related in: MedlinePlus

Histological characteristics of normal and osteosarcoma tissues.Notes: (A) Histological section of normal bone tissue of a mouse showing uniform arrangement of cells. (B) Primary osteosarcoma tissue with abnormal mass of cells. (C) Metastatic osteosarcoma tissue showing irregular cells that are enlarged in size when compared to normal cells. (D) Primary osteosarcoma tissue treated with SAM showing reversion in cellular pattern. (E) Metastatic osteosarcoma tissue treated with SAM showing no changes in cellular pattern. Scale bar: 100 µm.Abbreviation: SAM, S-adenosylmethionine.
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f1-ott-9-3653: Histological characteristics of normal and osteosarcoma tissues.Notes: (A) Histological section of normal bone tissue of a mouse showing uniform arrangement of cells. (B) Primary osteosarcoma tissue with abnormal mass of cells. (C) Metastatic osteosarcoma tissue showing irregular cells that are enlarged in size when compared to normal cells. (D) Primary osteosarcoma tissue treated with SAM showing reversion in cellular pattern. (E) Metastatic osteosarcoma tissue treated with SAM showing no changes in cellular pattern. Scale bar: 100 µm.Abbreviation: SAM, S-adenosylmethionine.

Mentions: In the present study, the mouse model of osteosarcoma was successfully initiated by injecting highly tumorigenic and metastatic osteosarcoma-forming K7M2 cells. The experimental mice responded well to injected K7M2 cells, which were examined through histological observation by comparing with the control mice (Figure 1A–C). Following injection, the mice were recognized with primary tumors, which were histologically visualized on the third week after injection of K7M2 cells (Figure 1B). Similarly, the metastatic condition of osteosarcoma was achieved on the fifth week after injection of K7M2 cells (Figure 1C). When compared with the control, which had an even arrangement of cells (Figure 1A), the primary and metastatic osteosarcoma cells were large and deeply stained together with a disorderly arrangement of cells (Figure 1B and C). The unique feature of the metastatic form (Figure 1C) is that it has an enlarged proliferative mass of cells with an irregular pattern of tissue arrangement compared to primary osteosarcoma (Figure 1B). Also, some of the cells were displaced to such an extent that the gaps between the clumps of cells were visible (Figure 1C). Upon SAM administration as described in the “Materials and methods” section, there was a remarkable improvement with reduction of proliferative cells, which is evident from the histological observation of primary osteosarcoma (Figure 1D) when compared with nontreated primary osteosarcoma (Figure 1B). But no positive improvement was observed in SAM-treated metastatic osteosarcoma (Figure 1E) as was analyzed with nontreated metastatic osteosarcoma (Figure 1C). From that, it was obvious that SAM has a positive effect in the primary stage of osteosarcoma.


Potential role of S-adenosylmethionine in osteosarcoma development.

Shi H, Mu WD, Zhang B, Meng T, Zhang ST, Zhou DS - Onco Targets Ther (2016)

Histological characteristics of normal and osteosarcoma tissues.Notes: (A) Histological section of normal bone tissue of a mouse showing uniform arrangement of cells. (B) Primary osteosarcoma tissue with abnormal mass of cells. (C) Metastatic osteosarcoma tissue showing irregular cells that are enlarged in size when compared to normal cells. (D) Primary osteosarcoma tissue treated with SAM showing reversion in cellular pattern. (E) Metastatic osteosarcoma tissue treated with SAM showing no changes in cellular pattern. Scale bar: 100 µm.Abbreviation: SAM, S-adenosylmethionine.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4920229&req=5

f1-ott-9-3653: Histological characteristics of normal and osteosarcoma tissues.Notes: (A) Histological section of normal bone tissue of a mouse showing uniform arrangement of cells. (B) Primary osteosarcoma tissue with abnormal mass of cells. (C) Metastatic osteosarcoma tissue showing irregular cells that are enlarged in size when compared to normal cells. (D) Primary osteosarcoma tissue treated with SAM showing reversion in cellular pattern. (E) Metastatic osteosarcoma tissue treated with SAM showing no changes in cellular pattern. Scale bar: 100 µm.Abbreviation: SAM, S-adenosylmethionine.
Mentions: In the present study, the mouse model of osteosarcoma was successfully initiated by injecting highly tumorigenic and metastatic osteosarcoma-forming K7M2 cells. The experimental mice responded well to injected K7M2 cells, which were examined through histological observation by comparing with the control mice (Figure 1A–C). Following injection, the mice were recognized with primary tumors, which were histologically visualized on the third week after injection of K7M2 cells (Figure 1B). Similarly, the metastatic condition of osteosarcoma was achieved on the fifth week after injection of K7M2 cells (Figure 1C). When compared with the control, which had an even arrangement of cells (Figure 1A), the primary and metastatic osteosarcoma cells were large and deeply stained together with a disorderly arrangement of cells (Figure 1B and C). The unique feature of the metastatic form (Figure 1C) is that it has an enlarged proliferative mass of cells with an irregular pattern of tissue arrangement compared to primary osteosarcoma (Figure 1B). Also, some of the cells were displaced to such an extent that the gaps between the clumps of cells were visible (Figure 1C). Upon SAM administration as described in the “Materials and methods” section, there was a remarkable improvement with reduction of proliferative cells, which is evident from the histological observation of primary osteosarcoma (Figure 1D) when compared with nontreated primary osteosarcoma (Figure 1B). But no positive improvement was observed in SAM-treated metastatic osteosarcoma (Figure 1E) as was analyzed with nontreated metastatic osteosarcoma (Figure 1C). From that, it was obvious that SAM has a positive effect in the primary stage of osteosarcoma.

Bottom Line: The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease.In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression.At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP.

View Article: PubMed Central - PubMed

Affiliation: Department of Traumatic Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan; Department of Bone and Joint Surgery.

ABSTRACT
The metastatic form of osteosarcoma is a life threatening one since it metastasizes to the lungs. The major cause of metastatic osteosarcoma is hypomethylation of numerous genes that undergo overexpression to enable the progression of the disease. In the present study, S-adenosylmethionine (SAM), a predominant methyl donor, was administered to find out its effects on osteosarcoma progression. As evidence of tumor suppression, the SAM-treated mouse tissue was analyzed histologically, which exemplifies the control that SAM has over abnormal cell proliferation, especially on primary osteosarcoma, but it lacks positive effects on metastatic osteosarcoma. At the molecular level, the successful inhibition of primary osteosarcoma was found to be associated with a lower expression of Sox2, a protein highly expressed in osteosarcoma stem cells, along with an upregulated expression of TCTP. The data suggest that the administration of SAM has a positive role in treating primary osteosarcoma, but it has no role in suppressing metastatic osteosarcoma. The decreased expression of Sox2 together with upregulation of TCTP following SAM administration indicates that SAM has a control over primary osteosarcoma.

No MeSH data available.


Related in: MedlinePlus